This application for a Mentored Research Career Development Award proposes a 5-year career plan for the PI to develop into an independent researcher who will contribute on a national level to understanding risk factors for cognitive decline in older African-American and Caucasian adults. Through a program of mentoring, consultation, coursework, hands-on training, and directed readings, the PI will study the influence of dietary and genetic antioxidant risk factors and their interaction on cognitive decline. Specifically, the candidate will develop expertise in 1) the epidemiology of cognitive decline and dementia; 2) nutritional epidemiology, particularly dietary and supplement intake of antioxidants; 3) molecular epidemiology, particularly genetic polymorphisms and dietary biomarkers; and 4) advanced methods for longitudinal data analyses. The PI's long-term career goal is to build on the expertise and collaborations developed during this KO1 to 1) examine other longitudinal studies that have collected biological samples, nutritional data, and cognitive data, but have not explored antioxidant risk factors and cognitive decline; 2) add cognitive assessments to ongoing studies that have collected dietary data and biological samples, but have not collected cognitive data; and 3) develop research studies to examine genetic and environmental risk factors in populations at high risk for cognitive decline. The overall hypothesis of the proposed studies is that cognitive decline is associated with low antioxidant intake and with genetic polymorphisms that modify this association. To address this hypothesis, the proposed research will focus on three specific aims: 1) examine the relationship of dietary and supplemental intake of antioxidants with cognitive decline; 2) examine the relationship between cognitive decline and specific genetic polymorphisms related to oxidative stress, including apolipoprotein-E, myeloperoxidase, manganese superoxide dismutase, and glutathione peroxidase; and 3) determine whether associations of antioxidant risk factors and cognitive decline are modified by genetic risk. These aims will be addressed in the Healthy Aging and Body Composition (HEALTH ABC) cohort, a 7-year, 2-site study of 3,075 adults (41.77/0 African-American and 58.3 percent Caucasian) aged 70-79 years at baseline.